Parkinson DiseaseAADCTDCNCT05558787
AADC/TDC in Advanced Parkinson's Disease
An observational study of Parkinson Disease, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Rationale: Many persons with Parkinson's disease (PD) develop a progressive resistance to levodopa, which is the pharmacological mainstay of PD treatment. Recently, two enzymatic pathways have been identified that could be (partially) responsible for this: 1) breakdown of levodopa by bacterial tyrosine decarboxylase… Read more about this study
- Who is it for?
- Ages 25 years and older
- Conditions the study is for
- Parkinson Disease
- How many people
- 48 participants
- Where
- 1 siteNetherlands
- Study dates
- 28 Jun 2023to 14 Aug 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 50 adult patients with Parkinson's disease (diagnosed by a neurologist), with a disease duration of at least 5 years (since diagnosis).
Who may be able to join
- Participant has Parkinson's disease of at least 5 years duration, defined as time since diagnosis made by a neurologist;
- Participant is an adult, at least 25 years of age;
- Participant can read and understand Dutch;
- Participant has completed the Ethics Committee-approved Informed Consent;
- Participant is willing, competent, and able to comply with all aspects of the protocol, including not taking their PD medication during a 12-hour period, and biospecimen collection.
Who cannot join
- Co-morbidities that would hamper interpretation of parkinsonian disability, such as coincident musculoskeletal abnormalities, as judged by the investigators;
- Significant doubt over the correctness of the diagnosis PD, as judged by the investigators;
- Not able to stand or walk without the assistance of another person (walking aids are not an exclusion criterion);
- Never having used levodopa;
- No current use of levodopa due to lack of effect, despite never having used at least 600mg/day during at least 1 month;
- Documented allergic reaction or severe side effect to levodopa or benserazide;
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- History of narrow-angle glaucoma (unless specific permission by the treating ophthalmologist for use of levodopa/benserazide);
- History of malignant melanoma (unless specific permission by the treating dermatologist for use of levodopa/benserazide);
- History of psychiatric disease with a psychotic component (unless specific permission by the treating psychiatrist for use of levodopa/benserazide);
- Known current uncompensated cardiovascular, endocrine, renal, hepatic, hematologic, or pulmonary disease (unless specific permission by the treating physician for use of levodopa/benserazide);
- Documented severe and debilitating dyskinesias on levodopa, to such an extent that levodopa treatment was terminated;
- Current pregnancy or breastfeeding;
- Co-morbidity with primary gastrointestinal pathology associated with altered gut microbiota and/or altered absorption (such as inflammatory bowel disease, celiac disease, colorectal carcinoma);
- Antibiotic use at any time during the 12 months leading up to the clinic visit;
- Current or recent (less than 1 month before clinic visit) use of (non-parkinson) drugs known or suspected to influence AADC activity, including amphetamine, dexamethasone, dopamine receptor antagonists, monoamine oxidase (MAO) inhibitors (including MAO-B inhibitors which are infrequently used as antiparkinsonian drugs), prostaglandin E2, and vigabatrin.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Radboudumc Centre of Expertise for Parkinson & Movement Disorders
Nijmegen, 6525 GC
About this study
Official title: Aromatic L-amino Acid Decarboxylase Activity, Tyrosine Decarboxylase Activity and Gut Microbiome in Patients With Advanced Parkinson's Disease
Rationale: Many persons with Parkinson's disease (PD) develop a progressive resistance to levodopa, which is the pharmacological mainstay of PD treatment. Recently, two enzymatic pathways have been identified that could be (partially) responsible for this: 1) breakdown of levodopa by bacterial tyrosine decarboxylase (TDC), an enzyme which normally decarboxylates dietary tyrosine but which is also able to decarboxylate levodopa. Accumulation of bacterial TDC in the small intestine, such as in the context of small-intestinal bacterial overgrowth (SIBO) - for which persons with PD are at increased risk - has the potential to prematurely metabolize levodopa, hence limiting its bioavailability and effect. 2) paradoxical induction of activity of the enzyme aromatic L-amino acid decarboxylase (AADC) in chronic users of levodopa combined with a peripheral decarboxylase inhibitor, also leading to a premature breakdown of levodopa and limitation of its bioavailability and effect.
Primary objective: in a cross-sectional sample of advanced (≥5 years) Parkinson's disease determining the prevalence of increased bacterial TDC activity in feces, and the prevalence of increased AADC activity in serum.
Read more
Secondary objective: correlating these biomarkers to clinical parameters, correlating composition of the microbiome to TDC activity, to the presence of levodopa resistance, and to factors related to socio-economic status.
Study design: using feces, serum and urine samples and clinical data from n=50 participants, the relevant enzymes' activity will be measured and the composition of the gut microbiome will be determined. These will be correlated to the clinical and demographic parameters.
- Conditions
- Parkinson Disease
- Medical subject headings
- Parkinson Disease
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevalence of increased TDC activity in feces
Measured: through study completion, an average of 2 weeks
Prevalence of increased AADC activity in serum
Measured: through study completion, an average of 2 weeks
Secondary outcomes (13)
Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III
Baseline score and score after levodopa administration
Measured: through study completion, an average of 2 weeks
Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part IV
Baseline score and score after levodopa administration
Measured: through study completion, an average of 2 weeks
Timed up-and-go test
TUG. Baseline score and score after levodopa administration
Measured: through study completion, an average of 2 weeks
Purdue Pegboard Test
Baseline score and score after levodopa administration
Measured: through study completion, an average of 2 weeks
Composite Clinical Motor Score
This is a composite of MDS-UPDRS-III, TUG and pegboard test scores. Baseline score and score after levodopa administration.
Measured: through study completion, an average of 2 weeks
modified Hoehn & Yahr score
Ordinal scale of Parkinson's disease severity. Baseline score and score after levodopa administration.
Measured: through study completion, an average of 2 weeks
9-item Wearing-Off Questionaire (WOQ-9)
Questionnaire on wearing-off symptoms
Measured: through study completion, an average of 2 weeks
SIBO questionnaire
15-item scale on gastrointestinal symptoms associated with small-intestinal bacterial overgrowth (SIBO)
Measured: through study completion, an average of 2 weeks
Schwab and England Activities of Daily Living Scale
Single-question scale on the ability to perform activities of daily living
Measured: through study completion, an average of 2 weeks
Medication questionnaire
9-item questionnaire on (current and past) medication use for Parkinson's disease, and their effect on symptoms
Measured: through study completion, an average of 2 weeks
Demographics questionnaire
14-item questionnaire on demographic parameters
Measured: through study completion, an average of 2 weeks
Diet questionnaire
18-item questionnaire on diet
Measured: through study completion, an average of 2 weeks
Prevalence of increased COMT activity in urine
Catechol-O-methyltransferase
Measured: through study completion, an average of 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2022
- Study start28 Jun 2023
- Primary completion14 Aug 2024
- Study completion14 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of Groningen, Predica Diagnostics, ParkinsonNL, Maag Lever Darm Stichting, Stichting Woelse Waard, Stichting Alkemade-Keuls
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05558787
- Sponsor's protocol ID
- 113707
- Acronym
- AADCTDC
- Status last verified
- Aug 2024
- First submitted
- 9 Sep 2022
- Last updated
- 19 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Aromatic L-amino Acid Decarboxylase Activity, Tyrosine Decarboxylase Activity and Gut Microbiome in Patients With Advanced Parkinson's Disease
- ClinicalTrials.gov ID
- NCT05558787
- Acronym / sponsor ID
- AADCTDC / 113707
- Conditions
- Parkinson Disease
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- University of Groningen, Predica Diagnostics, ParkinsonNL, Maag Lever Darm Stichting, Stichting Woelse Waard, Stichting Alkemade-Keuls
- Study start
- 28 Jun 2023 (actual)
- Primary completion
- 14 Aug 2024 (actual)
- Study completion
- 14 Aug 2024 (actual)
- First posted
- 28 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Rationale: Many persons with Parkinson's disease (PD) develop a progressive resistance to levodopa, which is the pharmacological mainstay of PD treatment. Recently, two enzymatic pathways have been identified that could be (partially) responsible for this: 1) breakdown of levodopa by bacterial tyrosine decarboxylase (TDC), an enzyme which normally decarboxylates dietary tyrosine but which is also able to decarboxylate levodopa. Accumulation of bacterial TDC in the small intestine, such as in the context of small-intestinal bacterial overgrowth (SIBO) - for which persons with PD are at increased risk - has the potential to prematurely metabolize levodopa, hence limiting its bioavailability and effect. 2) paradoxical induction of activity of the enzyme aromatic L-amino acid decarboxylase (AADC) in chronic users of levodopa combined with a peripheral decarboxylase inhibitor, also leading to a premature breakdown of levodopa and limitation of its bioavailability and effect.
Primary objective: in a cross-sectional sample of advanced (≥5 years) Parkinson's disease determining the prevalence of increased bacterial TDC activity in feces, and the prevalence of increased AADC activity in serum.
Secondary objective: correlating these biomarkers to clinical parameters, correlating composition of the microbiome to TDC activity, to the presence of levodopa resistance, and to factors related to socio-economic status.
Study design: using feces, serum and urine samples and clinical data from n=50 participants, the relevant enzymes' activity will be measured and the composition of the gut microbiome will be determined. These will be correlated to the clinical and demographic parameters.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 25 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 50 adult patients with Parkinson's disease (diagnosed by a neurologist), with a disease duration of at least 5 years (since diagnosis).
Key inclusion criteria (5 listed)
- Participant has Parkinson's disease of at least 5 years duration, defined as time since diagnosis made by a neurologist;
- Participant is an adult, at least 25 years of age;
- Participant can read and understand Dutch;
- Participant has completed the Ethics Committee-approved Informed Consent;
- Participant is willing, competent, and able to comply with all aspects of the protocol, including not taking their PD medication during a 12-hour period, and biospecimen collection.
Key exclusion criteria (15 listed)
- Co-morbidities that would hamper interpretation of parkinsonian disability, such as coincident musculoskeletal abnormalities, as judged by the investigators;
- Significant doubt over the correctness of the diagnosis PD, as judged by the investigators;
- Not able to stand or walk without the assistance of another person (walking aids are not an exclusion criterion);
- Never having used levodopa;
- No current use of levodopa due to lack of effect, despite never having used at least 600mg/day during at least 1 month;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Prevalence of increased TDC activity in feces
Time frame: through study completion, an average of 2 weeks
Prevalence of increased AADC activity in serum
Time frame: through study completion, an average of 2 weeks
13 secondary outcomes
Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III
Time frame: through study completion, an average of 2 weeks
Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part IV
Time frame: through study completion, an average of 2 weeks
Timed up-and-go test
Time frame: through study completion, an average of 2 weeks
Purdue Pegboard Test
Time frame: through study completion, an average of 2 weeks
Composite Clinical Motor Score
Time frame: through study completion, an average of 2 weeks
modified Hoehn & Yahr score
Time frame: through study completion, an average of 2 weeks
9-item Wearing-Off Questionaire (WOQ-9)
Time frame: through study completion, an average of 2 weeks
SIBO questionnaire
Time frame: through study completion, an average of 2 weeks
Schwab and England Activities of Daily Living Scale
Time frame: through study completion, an average of 2 weeks
Medication questionnaire
Time frame: through study completion, an average of 2 weeks
Demographics questionnaire
Time frame: through study completion, an average of 2 weeks
Diet questionnaire
Time frame: through study completion, an average of 2 weeks
Prevalence of increased COMT activity in urine
Time frame: through study completion, an average of 2 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Parkinson Disease, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prevalence of increased TDC activity in feces (time frame: through study completion, an average of 2 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2024.